Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors
This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in patients with mesothelioma and/or metastatic solid tumors that are resistant to standard therapy or for which no effective standard therapy is available.
Study details:
Dose escalation (Part 1) will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with metastatic solid tumors or mesothelioma. The 3 + 3 design will be implemented until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The MTD is defined as the highest dose level at which \< 33% of patients experience a dose limiting toxicity (DLT) during the first cycle of the study (Cycle 1).
Dose Expansion (Part 2) will further evaluate the safety and assess preliminary antitumor activity at the recommended phase 2 dose(s) and schedule(s) with up to 6 cohorts. Expansion cohorts 1 and 2 will enroll patients with mesothelioma of any site origin with or without NF2 mutations. Expansion cohort 3 will enroll non-pleural mesothelioma patients.
Expansion cohort 4 will enroll solid tumor patients with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements. Cohort 5 will enroll pleural mesothelioma patients. Combination part (Part 3) includes two cohorts.
Cohort A will enroll mesothelioma patients who will receive VT3989 in combination with immunotherapy (nivolumab plus ipilimumab). Cohort B will enroll NSCLC patients whose tumors have exon 19 deletion or exon 21 L858R mutation and will receive VT3989 in combination with targeted therapy (Osimertinib).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Part 1: Patients with pathologically diagnosed metastatic solid tumor or mesothelioma who have progressed on or after all approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
- Part 2 Expansion Cohorts 1 and 2: In mesothelioma cohorts, patients with pathologically diagnosed advanced malignant mesothelioma with or without NF2 mutations, who have progressed on or after all approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
- Part 2 Expansion Cohort 3: Only non-pleural mesothelioma patients with epithelioid histology, who have relapsed from or are refractory to prior platinum-based chemotherapy and immunotherapy.
- Part 2 Expansion Cohort 4: in the solid tumor cohort, patients with pathologically diagnosed metastatic or locally advanced solid tumor with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements, who have progressed on or after approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
- Part 2 Expansion Cohort 5: Patients with pathologically diagnosed advanced malignant pleural mesothelioma with epithelioid histology, who have progressed on or after licensed immunotherapy, chemotherapy or combined chemoimmunotherapy, except if the patient refuses or is not a candidate for such therapy.
- Part 3 Combination Cohort A: Patients with pathologically diagnosed, metastatic or unresectable malignant mesothelioma (including both pleural and non-pleural) who have not received systemic therapy.
- Part 3 Combination Cohort B: Patients with pathologically diagnosed incurable locally advanced (inoperable or recurrent), or metastatic NSCLC with exon 19 deletions or exon 21 L858R mutations, with or without prior treatment with Osimertinib.
- Part 1: Evaluable or measurable disease per RECIST v1.1 or mRECIST
- Part 2 and 3: Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors or modified RECIST v1.1 for malignant pleural mesothelioma. mRECIST may be used for pleural extension of non-pleural mesothelioma or for mixed pleural and peritoneal (or other) mesothelioma.
- ECOG: 0-1.
- Adequate organ functions, including the liver, kidneys, and hematopoietic system.
Exclusion criteria
- Active brain metastases or primary CNS (central nervous system) tumors.
- History of leptomeningeal metastases
- Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Known HIV positive or active Hepatitis B or Hepatitis C
- Clinically significant cardiovascular disease
- Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula); except for Part 2 Expansion Cohort 3, the QTcF interval criteria is > 450 msec).
- Additional active malignancy that may confound the assessment of the study endpoints
- Women who are pregnant or breastfeeding
- Prior treatment with TEAD inhibitor, except for EHE patients.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT04665206
Intervention or treatment
DRUG: VT3989
DRUG: Nivolumab & Ipilimumab
DRUG: Osimertinib
Conditions
- Solid Tumor, Adult
- Mesothelioma
- NSCLC
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Research sites nearby
Closest Location:
Monash Health
Select from list below to view details:
Monash Health
Clayton, Victoria, Australia
Peter MacCullum Cancer Centre
Melbourne, Victoria, Australia
Linear Clinical Research
Nedlands, Western Australia, Australia
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Who is running the clinical trial?
Vivace Therapeutics, Inc
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: VT3989 Dose Escalation [Not Recruiting]
| Drug: VT3989 |
EXPERIMENTAL: Dose Expansion [Not Recruiting]
| Drug: VT3989 |
EXPERIMENTAL: Combination [Recruiting]
| Drug: VT3989, Drug: Nivolumab & Ipilimumab, Drug: Osimertinib, Drug: Pemetrexed/Carboplatin |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Dose Limiting Toxicity | Incidence of Adverse and Serious Adverse Events | over the first 21 days of dosing |
| Occurrence of General Toxicity | Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety evaluations | through study completion, an average of 30 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Response | Determined by RECIST v1.1 or modified RECIST v1.1 | through study completion, an average of 30 months |
| Pharmacokinetic Evaluation - Cmax | Peak plasma concentration of VT3989 | for first 6 cycles |
| Pharmacokinetic Evaluation - Tmax | Time to reach peak plasma concentration of VT3989 | for first 6 cycles |
| Pharmacokinetic Evaluation - Half-life | Time required for the plasma concentration of VT3989 to reduce by half after reaching peak | for first 6 cycles |
| Overall survival (Part 2, expansion cohort 3, 4, and 5) | The overall survival of the enrolled patients from starting VT3989 treatment | Through study completion, an average of 30 months |
| Progression free survival (Part 2, expansion cohort 3, 4, and 5) | The progression free survival of the enrolled patients from starting VT3989 treatment | Through study completion, an average of 30 months |
| Quality of life assessment (Part 2, expansion cohort 3, 4, and 5) | Assessing the Quality of life changes via patient reported outcomes | Through study completion, an average of 30 months |
References
Clinical Trials Gov: Study to Evaluate VT3989 in Patients With Metastatic Solid TumorsOther trials to consider
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